Sandwich-like reduced graphene oxide/yolk-shell-structured Fe@Fe3O4/carbonized paper as an efficient freestanding electrode for electrochemical synthesis of ammonia directly from H2O and nitrogen.
Ammonia is an important raw material in the fertilizer industry and a promising H-based fuel. However, its synthesis still largely relies on the conventional Haber-Bosch process, which is not only energy-consuming, but also environmentally damaging. Alternatively, the electrochemical synthesis of ammonia has drawn considerable interest. Herein, sandwich-like reduced graphene oxide/yolk-shell-structured Fe@Fe3O4/carbonized paper has been synthesized and employed as a freestanding electrode for nitrogen reduction reaction at room temperature and atmospheric pressure. The electrocatalytic measurements show that the as-obtained freestanding electrode exhibits high electrocatalytic activity (NH3 formation rate of 1.3 × 10-10 mol cm-2 s-1), excellent selectivity (faradaic efficiency of 6.25%), and good stability, which are equivalent to (or even higher than) those of previously reported noble metal-based catalysts under comparable reaction conditions. The superior electrocatalytic performance of the rGO/Fe@Fe3O4/CP freestanding cathode for electrochemical synthesis of ammonia is mainly attributed to its unique sandwich-like nanoarchitecture with the middle yolk-shell-structured Fe@Fe3O4 nanoparticles and the synergistic effect between rGO and Fe@Fe3O4.


Quality assurance in human molecular genetics testing: status and recommendations.
The role of genetic testing has expanded with rapidly developing technology and completion of the International Human Genome Project. Development of universally acceptable quality control methods and quality assurance standards trails technology. The principle that high-quality genetic testing is important for public health motivated the Centers for Disease Control and Prevention to formulate ways for improving quality assurance of human molecular genetics testing. Twenty-eight panelists were chosen based on expertise in molecular genetics testing and knowledge of quality assurance practices. Representatives of professional organizations, industries, and federal agencies participated in one or more of 3 panel meetings. Consensus recommendations were developed by the 15 panelists in the third meeting. Evidence was derived from experts' opinion during 3 panel meetings. Data compiled through laboratory visits and literature review were used as reference information. Need for this project was derived from the Final Report of the Task Force on Genetic Testing, produced by the National Institutes of Health and the Department of Energy in 1997, and the Summary Report of the Subcommittee Meeting on Genetics of the Clinical Laboratory Improvement Act Advisory Committee in 1997. Research and development needs were identified using a participatory visioning approach. A modified nominal group process was used to reach consensus. Five core consensus recommendations were made: research for developing positive samples for quality assurance purposes, performance evaluation programs supplementing those in existence, establishment and support of laboratory-oriented consortia, establishment of a laboratory-focused database, and support of molecular genetics training programs.


Structure of a second BRCT domain identified in the nijmegen breakage syndrome protein Nbs1 and its function in an MDC1-dependent localization of Nbs1 to DNA damage sites.
The Nijmegen breakage syndrome protein Nbs1 is a component of the MRN (Mre11-Rad50-Nbs1) complex, central to the DNA damage response. While Nbs1 is generally believed to encompass a forkhead-associated domain linked to a breast cancer C-terminal (BRCT) domain, to date there is no experimental information on its three-dimensional structure. Through nuclear magnetic resonance (NMR) three-dimensional structure determination, we demonstrate that there is a second BRCT domain (BRCT2) in Nbs1. The domain has the characteristic BRCT topology, but with a long insertion shown to be flexible by NMR relaxation measurements. In the absence of sequence similarity to other proteins, a search for structural analogs of BRCT2 returned the second BRCT domain of the tandem BRCT repeats of cell cycle checkpoint proteins MDC1 (mediator of DNA damage checkpoint protein 1) and BRCA1 (breast cancer protein 1), suggesting that like MDC1 and BRCA1, Nbs1 also possesses tandem BRCT domains with phosphoprotein binding ability. Structure-based single point mutations in human Nbs1 were evaluated in vivo and revealed that BRCT2 is essential for an MDC1-dependent relocalization of Nbs1 to DNA damage sites, most likely through a direct interaction of Nbs1 tandem BRCT domains with phosphorylated MDC1.


Analysis of volatile compounds from various types of barley cultivars.
We identified volatile compounds of barley flour and determined the variation in volatile compound profiles among different types and varieties of barley. Volatile compounds of 12 barley and two wheat cultivars were analyzed using solid phase microextraction (SPME) and gas chromatography. Twenty-six volatiles comprising aldehydes, ketones, alcohols, and a furan were identified in barley. 1-Octen-3-ol, 3-methylbutanal, 2-methylbutanal, hexanal, 2-hexenal, 2-heptenal, 2-nonenal, and decanal were identified as key odorants in barley as their concentration exceeded their odor detection threshold in water. Hexanal (46-1269 microg/L) and 1-pentanol (798-1811 microg/L) were the major volatile compounds in barley cultivars. In wheat, 1-pentanol (723-748 microg/L) was a major volatile. Hulled barley had higher total volatile, aldehyde, ketone, alcohol, and furan contents than hulless barley, highlighting the importance of the husk in barley grain aroma. The proanthocyanidin-free varieties generally showed higher total volatile and aldehyde contents than wild-type varieties, potentially due to decreased antioxidant activity by the absence of proanthocyanidins.


Anatomy and ecology of the shell-less endoparasitic gastropod Asterophila japonica Randall and Heath, 1912 (Mollusca: Eulimidae).
The shell-less, endoparasitic gastropod, Asterophila japonica , was collected from two species of sea star, Leptychaster anomalus Fisher, 1906 and Ctenodiscus crispatus (Retzius, 1805) in Toyama Bay, Japan. All observed individuals were located on the aboral side of the host's disk (except one specimen parasitizing the arm) between the epidermis and the coelomic epithelium. More than one large individual frequently co-occur on a single host. The body plan of A. japonica is surprisingly modified from that of general gastropods; organs unrelated to digestion and reproduction are greatly reduced, simplified or completely lost. Dimorphism of body size is striking between males and females: males are much smaller than females and are attached to the surface of the pseudopallium of females. Females deposit and brood an egg mass(es) in the pseudopallial cavity until the eggs develop to veliger larvae. At the late developmental stage, brooded larvae reduce the velum and develop the foot for crawling, suggesting lecithotrophic development with or without a short planktonic stage. It is uncertain as to how the larvae can find and parasitize the next generation of the host. The systematic placement of Asterophila in the family Eulimidae is supported by three characters, viz. parasitism on echinoderms, smooth hydrophobic protoconch, and the enclosure of the visceral mass with the pseudopallium.


Giant Dorsalis Pedis Pseudoaneurysm Following Cannulation for Arterial Line in a Patient with Systemic Lupus Erythematosus.
Dorsalis pedis artery (DPA) aneurysms are very rare and fewer than 60 cases have been reported in the literature. Most affected patients present with false aneurysms after orthopedic surgery or trauma. Here we report an unusual case of a giant DPA pseudoaneurysm after cannulation for arterial line placement in a patient newly diagnosed with systemic lupus erythematosus (SLE). A diagnostic delay resulted in necrosis of the overlying skin. Excision of the pseudoaneurysm, ligation of the DPA, and debridement of the foot dorsum were performed, followed by a second flap coverage surgery. Although a DPA false aneurysm is rare after arterial line removal, it can cause the serious complications of skin necrosis, rupture and toe necrosis. Arterial puncture sites should be carefully monitored, especially in patients with SLE or other vasculitis.


COLOR-PATTERN VARIATION IN LAKE ERIE WATER SNAKES: PREDICTION AND MEASUREMENT OF NATURAL SELECTION.
A classic example of natural selection, that of color-pattern variation in Lake Erie island populations of water snakes, was reexamined to overcome shortcomings resulting from classification of snakes into discrete color-pattern categories and use of cross-sectional data. Four continuously varying color-pattern components (DB, the number of dorsal blotches; LB, the number of lateral blotches; ROWS, the height of lateral blotches measured in scale rows; and VEXT, the extent of ventral pigmentation) were analyzed. Patterns of natural selection were predicted from the relationship between color-pattern scores and independent measures of relative crypsis. Tests for natural selection were carried out using longitudinal data on neonate to juvenile-aged snakes and cross-sectional data on juvenile to adult-aged snakes. As predicted, the form of selection differed between younger and older age classes of snakes: selection resulted in a reduction in DB and LB among neonate and juvenile snakes but had little influence on color-pattern components in older snakes. The correspondence between observed patterns of natural selection and predictions based on the relationship between color-pattern scores and relative crypsis supports the hypothesis that differential predation by visual predators on younger age classes of snakes is the mechanism of selection. Gene flow from mainland populations or the initial lack of an allele necessary for reduced pattern may explain why selection has not resulted in greater differentiation between island and mainland populations.


The DSL ligand APX-1 is required for normal ovulation in C. elegans.
DSL ligands activate the Notch receptor in many cellular contexts across metazoa to specify cell fate. In addition, Notch receptor activity is implicated in post-mitotic morphogenesis and neuronal function. In C. elegans, the DSL family ligand APX-1 is expressed in a subset of cells of the proximal gonad lineage, where it can act as a latent proliferation-promoting signal to maintain proximal germline tumors. Here we examine apx-1 in the proximal gonad and uncover a role in the maintenance of normal ovulation. Depletion of apx-1 causes an endomitotic oocyte (Emo) phenotype and ovulation defects. We find that lag-2 can substitute for apx-1 in this role, that the ovulation defect is partially suppressed by loss of ipp-5, and that lin-12 depletion causes a similar phenotype. In addition, we find that the ovulation defects are often accompanied by a delay of spermathecal distal neck closure after oocyte entry. Although calcium oscillations occur in the spermatheca, calcium signals are abnormal when the distal neck does not close completely. Moreover, oocytes sometimes cannot properly transit through the spermatheca, leading to fragmentation of oocytes once the neck closes. Finally, abnormal oocytes and neck closure defects are seen occasionally when apx-1 or lin-12 activity is reduced in adult animals, suggesting a possible post-developmental role for APX-1 and LIN-12 signaling in ovulation.


[Anaesthetic management of patients with hyperdynamic circulation in hepatic cirrhosis (author's transl)].
Cirrhosis of the liver is frequently associated with arterial hypoxaemia and a hyperdynamic state of the systemic circulation. The hypoxaemia and the circulatory changes probably have a common aetiology, namely, shynting in the systemic and pulmonary vascular beds. Experiences in two well-documented cases suggest that anaesthetic agents may increase arteriovenous shunting and hypoxaemia in patients with hepatic cirrhosis. A plan for preanaesthetic identification and anaesthetic management in this type of patients is outlined.


Irreversible post-translational modifications - Emerging cardiovascular risk factors.
Despite the introduction of lipid-lowering drugs, antihypertensives, antiplatelet and anticoagulation therapies for primary prevention of cardiovascular and heart diseases (CVD), it remains the number one cause of death globally, raising the question for novel/further essential factors besides traditional risk factors such as cholesterol, blood pressure and coagulation. With continuous identification and characterization of non-enzymatic post-translationally modified isoforms of proteins and lipoproteins, it is becoming increasingly clear that irreversible non-enzymatic post-translational modifications (nPTMs) alter the biological functions of native proteins and lipoproteins thereby transforming innate serum components into CVD mediators. In particular renal insufficiency and metabolic imbalance are major contributors to the systemically increased concentration of reactive metabolites and thus increased frequency of nPTMs, promoting multi-morbid disease development centering around cardiovascular disease. nPTMs are significantly involved in the onset and progression of cardiovascular disease and represent a significant and novel risk factor. These insights represent potentially new avenues for risk assessment, prevention and therapy. This review chapter summarizes all forms of nPTMs found in CKD and under metabolic imbalance and discusses the biochemical connections between molecular alterations and the pathological impact on increased cardiovascular risk, novel nPTM-associated non-traditional cardiovascular risk factors, and clinical implication of nPTM in cardiovascular disease.


[The arrival of the "grand pox" at the hôtel-Dieu de Lyon].
Founded in 542, the Hospital hôtel-Dieu in Lyons is considered as the oldest French Hospital. At the beginning it was a place to receive and assist the poor and pilgrims and in the middle of the XVth century it received infectious patients during some epidemic periods. As King Charles VIII came back from Naples his troops suffering from syphilis arrived in Lyons in October 1495 and were treated in the Hospital hôtel-Dieu so that it became the first French Hospital to treat syphilitic patients. On the 7th of July 1496, a request of the "Consulat" gave the first information mentioned about syphilitic soldiers in Lyons and the well-known French physician Symphorien Champier was the first to publish about syphilis. For three centuries the Hospital hôtel-Dieu tried to move away syphilitic patients and it succeeded in 1802 as the Hospital L'Antiquaille was built.


Genetic Simulation Resources: a website for the registration and discovery of genetic data simulators.
Many simulation methods and programs have been developed to simulate genetic data of the human genome. These data have been widely used, for example, to predict properties of populations retrospectively or prospectively according to mathematically intractable genetic models, and to assist the validation, statistical inference and power analysis of a variety of statistical models. However, owing to the differences in type of genetic data of interest, simulation methods, evolutionary features, input and output formats, terminologies and assumptions for different applications, choosing the right tool for a particular study can be a resource-intensive process that usually involves searching, downloading and testing many different simulation programs. Genetic Simulation Resources (GSR) is a website provided by the National Cancer Institute (NCI) that aims to help researchers compare and choose the appropriate simulation tools for their studies. This website allows authors of simulation software to register their applications and describe them with well-defined attributes, thus allowing site users to search and compare simulators according to specified features. http://popmodels.cancercontrol.cancer.gov/gsr.


A comparison of two different team models for treatment of diabetes mellitus in primary care.
The importance of the nurse's role in the management of patients with type 2 diabetes has long since been emphasized. The aim of this study was to test the hypothesis that a structured organization of type 2 diabetes care, with a diabetes nurse working more independently of the general practitioner, has a significant impact on the patient's self-management and quality of care. The test consisted of 394 registered patients, all with an onset of diabetes mellitus occurring after the age of 34, at two primary health care (PHC) districts in Blekinge county in South Sweden. During one year all consultations for both doctors and nurses were analysed, and a structured telephone survey was carried out involving 364 patients who were 84 years or younger. A comparison between the two PHC centres was made regarding quality of care, frequency of consultation, patients' knowledge of their disease, and patients' self-management. The results showed that organizing care of type 2 diabetes in a structured way encourages better metabolic control in spite of less use of oral medication, and among the patients a greater knowledge of their disease and a more active self-management thus favouring implementation of local guidelines. Also, a difference was found in the patients' choice of contact with doctor or nurse regarding their diabetes and even other causes, which shifted the balance from doctor to nurse. This study provides support for organizing type 2 diabetes care in a structured way to increase the quality of care.


Development of a new carbon nanotube-alginate-hydroxyapatite tricomponent composite scaffold for application in bone tissue engineering.
In recent times, tricomponent scaffolds prepared from naturally occurring polysaccharides, hydroxyapatite, and reinforcing materials have been gaining increased attention in the field of bone tissue engineering. In the current work, a tricomponent scaffold with an oxidized multiwalled carbon nanotube (fMWCNT)-alginate-hydroxyapatite with the required porosity was prepared for the first time by a freeze-drying method and characterized using analytical techniques. The hydroxyapatite for the scaffold was isolated from chicken bones by thermal calcination at 800°C. The Fourier transform infrared spectra and X-ray diffraction data confirmed ionic interactions and formation of the fMWCNT-alginate-hydroxyapatite scaffold. Interconnected porosity with a pore size of 130-170 µm was evident from field emission scanning electron microscopy. The total porosity calculated using the liquid displacement method was found to be 93.85%. In vitro biocompatibility and cell proliferation on the scaffold was checked using an MG-63 cell line by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell attachment by Hoechst stain assay. In vitro studies showed better cell proliferation, cell differentiation, and cell attachment on the prepared scaffold. These results indicate that this scaffold could be a promising candidate for bone tissue engineering.


The microtubular cytoskeleton of the apusomonad Thecamonas, a sister lineage to the opisthokonts.
Apusomonads are of evolutionary interest because they are close relatives to the supergroup Opisthokonta, which contains both animals and fungi. There are no detailed morphological studies of 'amastigomonad' type apusomonads, such as Thecamonas trahens, despite this species having a sequenced genome. We use serial-section transmission electron microscopy and 3D reconstruction to examine the cell architecture and complete microtubular cytoskeleton of Thecamonas. Thecamonas has two flagella and an anteriorly projecting 'tusk'. The anterior basal body associates with one microtubular root, which travels leftward, and a non-root 'ribbon' of six microtubules that travels down the right side of the cell. The posterior basal body associates with three roots: an eight-membered right root, a doublet left root, and an intermediate singlet root. These rearrange into two bands, both on the left side of the cell. One comprises the left and singlet roots plus one right root microtubule. The other comprises the remaining right root microtubules. A splitting right root and supernumerary singlet root are also present in breviates, ancyromonads, and 'typical excavates', suggesting that these characters are ancestral for much of eukaryote diversity. If so, opisthokonts, and most or all living eukaryotes, probably arose from cells with complex microtubular cytoskeletons.


The effects of environmental temperature on fertility of the domestic fowl.
Three experiments were conducted to determine the influence of environmental temperature upon the fertility of domestic fowl. It was found that a cold environmental temperature depressed testes growth and delayed spermatogenesis in maturing cockerels. There was also a highly significant difference in the fertility of mature males kept at different environmental temperatures. Males kept at 19 degrees C. had higher fertility than males kept in either 30 degrees or 8 degrees C. The effects of environmental temperature on female fertility was also studied. Fertility was significantly lower in the hens kept at 30 degrees C. than that of similar groups held at an environment of 8 degrees C.


[Ductal adenocarcinoma of the pancreas: subtypes and molecular pathology].
Ductal adenocarcinoma is the most common tumor of the pancreas. Although relatively rare, it poses one of the greatest oncological challenges because of its poor prognosis, which has so far only slightly improved. Progress has been made in the more precise classification and standardization of the morphological assessment. In the current WHO classification, prognostically relevant subtypes are clearly delimited among themselves and from ductal adenocarcinoma not otherwise specified (NOS). In the recent TNM classification, a size-based T‑category was introduced. Diagnostically, the histological assessment of the resection specimen is relatively easy; on the other hand, assessment of the fine-needle biopsy from the primary tumor or a liver metastasis is still difficult. The molecular stratification of ductal adenocarcinoma and the other pancreatic neoplasms has made great progress. This not only defined the genetics of tumor entities, but also identified the prognosis and biology of tumor groups on the basis of RNA expression patterns. The range of treatment could be expanded by targeted molecular therapies (especially for patients with BRCA1/2 germline mutations, NTRK- or NRG1-fusions, or oncogenic BRAF and PIK3CA mutations as well as tumors with microsatellite instability (MSI)), even if targeted therapies are currently only available for a minority of patients (<10%).


Verbatim and gist recall of sentences by dyslexic and non-dyslexic adults.
Forty-eight college students, 24 of them dyslexic, were presented with four sentences of increasing complexity. Participants were asked to repeat each sentence and a record was kept of the number of repetitions required before 100% correct accuracy was achieved. None of the 24 control participants required a total of more than eight repetitions over the four sentences, whereas among the dyslexics the total number of repetitions needed ranged from one to 25. Dyslexic participants were unpredictable in their performance from one level of difficulty to the next and inter-individual variability was far greater in the dyslexic group than in the control group. Overall, despite their relatively poor performance in achieving verbatim accuracy relative to non-dyslexic participants, dyslexic individuals regularly managed to preserve the gist of the sentences. Some theoretical issues arising from these results are discussed.


Management of patients presenting to the emergency department with sudden onset severe headache: systematic review of diagnostic accuracy studies.
Advances in imaging technologies have precipitated uncertainty and inconsistency in the management of neurologically intact patients presenting to the Emergency Department (ED) with non-traumatic sudden onset severe headache with a clinical suspicion of subarachnoid haemorrhage (SAH). The objective of this systematic review was to evaluate diagnostic strategies in these patients. Studies assessing any decision rule or diagnostic test for evaluating neurologically intact adults with a severe headache, reaching maximum intensity within 1 hour, were eligible. Eighteen databases (including MEDLINE and Embase) were searched. Quality was assessed using QUADAS-2. Where appropriate, hierarchical bivariate meta-analysis was used to synthesise diagnostic accuracy results. Thirty-seven studies were included. Eight studies assessing the Ottawa SAH clinical decision rule were pooled; sensitivity 99.5% (95% CI 90.8 to 100), specificity 24% (95% CI 15.5 to 34.4). Four studies assessing CT within 6 hours of headache onset were pooled; sensitivity 98.7% (95% CI 96.5 to 100), specificity 100% (95% CI 99.7 to 100). The sensitivity of CT beyond 6 hours was considerably lower (≤90%; 2 studies). Three studies assessing lumbar puncture (LP; spectrophotometric analysis) following negative CT were pooled; sensitivity 100% (95% CI 100 to 100), specificity 95% (95% CI 86.0 to 98.5). The Ottawa SAH Rule rules out further investigation in only a small proportion of patients. CT undertaken within 6 hours (with expertise of a neuroradiologist or radiologist who routinely interprets brain images) is highly accurate and likely to be sufficient to rule out SAH; CT beyond 6 hours is much less sensitive. The CT-LP pathway is highly sensitive for detecting SAH and some alternative diagnoses, although LP results in some false positive results.


Current status and progress in research on dressing management for diabetic foot ulcer.
Diabetic foot ulcer (DFU) is a major complication of diabetes and is associated with a high risk of lower limb amputation and mortality. During their lifetime, 19%-34% of patients with diabetes can develop DFU. It is estimated that 61% of DFU become infected and 15% of those with DFU require amputation. Furthermore, developing a DFU increases the risk of mortality by 50%-68% at 5 years, higher than some cancers. Current standard management of DFU includes surgical debridement, the use of topical dressings and wound decompression, vascular assessment, and glycemic control. Among these methods, local treatment with dressings builds a protective physical barrier, maintains a moist environment, and drains the exudate from DFU wounds. This review summarizes the development, pathophysiology, and healing mechanisms of DFU. The latest research progress and the main application of dressings in laboratory and clinical stage are also summarized. The dressings discussed in this review include traditional dressings (gauze, oil yarn, traditional Chinese medicine, and others), basic dressings (hydrogel, hydrocolloid, sponge, foam, film agents, and others), bacteriostatic dressings, composite dressings (collagen, nanomaterials, chitosan dressings, and others), bioactive dressings (scaffold dressings with stem cells, decellularized wound matrix, autologous platelet enrichment plasma, and others), and dressings that use modern technology (3D bioprinting, photothermal effects, bioelectric dressings, microneedle dressings, smart bandages, orthopedic prosthetics and regenerative medicine). The dressing management challenges and limitations are also summarized. The purpose of this review is to help readers understand the pathogenesis and healing mechanism of DFU, help physicians select dressings correctly, provide an updated overview of the potential of biomaterials and devices and their application in DFU management, and provide ideas for further exploration and development of dressings. Proper use of dressings can promote DFU healing, reduce the cost of treating DFU, and reduce patient pain.


QUANTITATIVE GENETIC ANALYSIS OF DIVERGENCE IN MALE SECONDARY SEXUAL TRAITS BETWEEN DROSOPHILA SIMULANS AND DROSOPHILA MAURITIANA.
The sibling species Drosophila simulans and D. mauritiana differ significantly in a number of male secondary sexual traits, providing an ideal system for genetic analysis of interspecific morphological divergence. In the experiment reported here, F1 hybrids from a cross of two inbred lines were backcrossed in both directions and about 200 flies from each backcross were scored for several traits (bristle numbers and cuticle areas), as well as 18 markers distributed throughout the genome. Each trait was analyzed by composite interval mapping to identify quantitative trait loci (QTL) and estimate their effects. For each trait, from one to eight loci were detected, with more divergent traits showing evidence for greater numbers of QTL. Estimates of additive effects varied widely, with a range of 0.4 to 4.1 environmental standard deviation units and an average of 2.2 units. There was substantial evidence for nonadditive effects, since the magnitude of estimates often differed significantly between the two backcrosses. The sign of the estimated effect differed among QTL for bristle traits, but not for cuticle area traits, suggesting that these two types of trait may have undergone different types of selection. Finally, several similarities were found between different traits in the estimated positions of QTL, suggesting that pleiotropy and/or linkage of QTL may have been important in the evolution of these traits.


Peripheral artery disease risk factors in Jeddah, Saudi Arabia: a retrospective study.
Peripheral artery disease (PAD) is a major health problem in Saudi Arabia with considerable implications for morbidity and mortality. Many risk factors have been established for developing PAD, but the prevalence of these risk factors is variable from one country to another. To identify the risk factors for PAD and study their prevalence in Jeddah, Saudi Arabia. A retrospective chart review study was conducted in a tertiary center in Jeddah from July 2012 to September 2015. All patients with PAD were recruited into this study, and their data were analyzed using IBM SPSS. Correlation between PAD and various risk factors was studied using Spearman's coefficient. A total of 261 patients were recruited, of which 55% were males. Hypertension, diabetes type 2, and obesity were found among 34.2%, 33.3%, and 29.2% of the patients, respectively. About 45% had a history of previous vascular surgery, and amputation was performed in 6.9% particularly in legs. Hypertension and metabolic syndrome were the only risk factors that showed a significant correlation with PAD (P=0.039 and 0.040, respectively). The most prevalent risk factors for PAD in Jeddah were hypertension, diabetes, obesity, and smoking. Hypertension and metabolic syndrome were the only risk factors significantly associated with PAD. Males were often more affected by PAD than females. The most commonly affected site was the lower limbs.


Observation of the Hadronic transitions chi(b1,2)(2P)-->omegaUpsilon(1S).
The CLEO Collaboration has made the first observations of hadronic transitions among bottomonium (bbmacr;) states other than the dipion transitions among Upsilon(nS) states. In our study of Upsilon(3S) decays, we find a significant signal for Upsilon(3S)-->gammaomegaUpsilon(1S) that is consistent with radiative decays Upsilon(3S)-->gammachi(b1,2)(2P), followed by chi(b1,2)(2P)-->omegaUpsilon(1S). The branching ratios we obtain are B[chi(b1)(2P)-->omegaUpsilon(1S)]=(1.63(+0.35+0.16)(-0.31-0.15))% and B[chi(b2)(2P)-->omegaUpsilon(1S)]=(1.10(+0.32+0.11)(-0.28-0.10))%, in which the first error is statistical and the second is systematic.


Synergistic activation of Src, ERK and STAT pathways in PBMCs for Staphylococcal enterotoxin A induced production of cytokines and chemokines.
Staphylococcal enterotoxin A (SEA) is a well-known superantigen and stimulates human peripheral blood mononuclear cells (PBMCs) involving in the pathogenesis of inflammatory disorders and cancer. To better understand the biological activities of SEA and the possible intracellular mechanisms by which SEA plays its roles in conditions like staphylococcal inflammatory and/or autoimmune disorders and immunotherapy. Recombinant SEA (rSEA) was expressed in a prokaryotic expression system and its effects on the cytokine and chemokine production was examined by Enzyme-linked Immunospot (ELISpot) Assay and ELISA analysis. In vitro experiments showed rSEA could significantly enhance secretion of a broad spectrum of cytokines and chemokines from PBMCs dose-dependently. Increased secretion of cytokines and chemokines from rSEA stimulated PBMCs was barely affected by C-C motif chemokine receptor 2 (CCR2) antagonist INCB3344. However, Src, ERK and STAT pathway inhibitors were able to successfully block the enhanced secretion of most of cytokines and chemokines produced by rSEA stimulated PBMCs. Our work suggested that rSEA serves as a potent stimulant of PBMCs, and induces the release of cytokines and chemokines through Src, ERK and STAT pathways upon a relatively independent network. Our work also strongly supported that Src, ERK and STAT signaling inhibitors could be effective therapeutic agents against diseases like toxic shock syndrome or infection by microbes resistant to antibiotics.


General anesthesia and the ketogenic diet: clinical experience in nine patients.
To determine if children actively on the ketogenic diet (KD) can safely undergo general anesthesia (GA) for surgical procedures. The records of children treated with the KD at Children's Hospital (Boston, Massachusetts) from 1995 to the present were reviewed. The charts of children who had received GA while on the diet were evaluated with regard to demographics, procedure information, anesthesia records, blood chemistries, and perioperative course. Of 71 children on the KD during the period of the study, nine (12.7%) had procedures requiring GA while on the diet. Nine children received GA for surgical procedures ranging from central line placement to hemispherectomy while on the KD. At the time of GA, the children ranged from age 1 to 6 years, and had been on the KD for 2-60 months. The patients received carbohydrate-free intravenous solutions perioperatively. Anesthesia duration ranged from 20 min to 11.5 h; for longer procedures, serum pH, glucose, and electrolyte levels were monitored. Serum glucose levels remained stable in all patients, but serum pH typically decreased; the largest reduction was to 7.16. In three procedures, patients received intravenous bicarbonate because of level of acidosis. There were no perioperative complications. Children on the KD can safely undergo GA for surgical procedures. Although serum glucose levels appear to remain stable, serum pH or bicarbonate levels should be monitored because of the risk of metabolic acidosis.


The Use of Oral Amino-Bisphosphonates and Coronavirus Disease 2019 (COVID-19) Outcomes.
The determinants of the susceptibility to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and severe coronavirus disease 2019 (COVID-19) manifestations are yet not fully understood. Amino-bisphosphonates (N-BPs) have anti-inflammatory properties and have been shown to reduce the incidence of lower respiratory infections, cardiovascular events, and cancer. We conducted a population-based retrospective observational cohort study with the primary objective of determining if oral N-BPs treatment can play a role in the susceptibility to development of severe COVID-19. Administrative International Classification of Diseases, Ninth Revision, Clinical ModificationI (ICD-9-CM) and anatomical-therapeutic chemical (ATC) code data, representative of Italian population (9% sample of the overall population), were analyzed. Oral N-BPs (mainly alendronate and risedronate) were included in the analysis, zoledronic acid was excluded because of the low number of patients at risk. Incidence of COVID-19 hospitalization was 12.32 (95% confidence interval [CI], 9.61-15.04) and 11.55 (95% CI, 8.91-14.20), of intensive care unit (ICU) utilization because of COVID-19 was 1.25 (95% CI, 0.38-2.11) and 1.42 (95% CI, 0.49-2.36), and of all-cause death was 4.06 (95% CI, 2.50-5.61) and 3.96 (95% CI, 2.41-5.51) for oral N-BPs users and nonusers, respectively. Sensitivity analyses that excluded patients with prevalent vertebral or hip fragility fractures and without concomitant glucocorticoid treatment yielded similar results. In conclusion, we found that the incidence of COVID-19 hospitalization, intensive care unit (ICU) utilization, and COVID-19 potentially related mortality were similar in N-BPs-treated and nontreated subjects. Similar results were found in N-BPs versus other anti-osteoporotic drugs. We provide real-life data on the safety of oral N-BPs in terms of severe COVID-19 risk on a population-based cohort. Our results do not support the hypothesis that oral N-BPs can prevent COVID-19 infection and/or severe COVID-19; however, they do not seem to increase the risk. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


[Purification and culture of astrocytes from cerebral cortex of neonatal rats in vitro].
To establish an effective method of primary and passage cultured cerebral cortical astrocyte of SD neonatal rat in vitro. Cerebral cortex of two 2-day-old SD rats were taken with aseptic operation and then were cut to pieces. After stripped the pia mater, digested by 500 μL 0. 25% trypsin at 37 ℃ for 15 min. Next, dispersed cell suspension was made by mechanical method and filtered. Cell suspensions were incubated in an uncoated culture bottle at 37 ℃ for 15 min. The cells were inoculated at 5×10~6/m L in the T75 culture flask coated with L-polylysine. The cells were shaken at 200 r/min 37 ℃ for 18 h, then added 1 m L of trypsin to digest cells and then collected the cells. The morphology of the passage cells was observed under inverted phase contrast microscope, and the purity of astrocytes was identified by immunofluorescence staining of GFAP. The proliferate activity of passage cells was determined by MTS assay. The purity of astrocytes was( 97. 86 ± 0. 91) %, and the growth and proliferation activity of astrocytes were good after passage. A rapid, economical and effective method for obtaining astrocytes in the cerebral cortex of newborn rats was established.


Kaposi's sarcoma of the oral cavity: case reports.
Classic Kaposi's sarcoma is a rare malignant neoplasm of endothelial cell origin. Oral manifestation of Kaposi's sarcoma is even more uncommon. The purpose of this article is to describe two cases of classic Kaposi's sarcoma and to discuss the current knowledge regarding its pathogenesis, epidemiology, clinical characteristics, and therapy.


The work and research of a single non-academic family physician.
This review of my own work over 30 years aims to help others decide whether they should and could pursue an interest in research in primary care. Lessons from failure are considered as well as how to be opportunistic in research. I suggest audit is a good place to start research as it requires several of the same disciplines. The difficult issue of working successfully with others is addressed along with a publication strategy. I illustrate some of the advantages and disadvantages of undertaking research from general practice. Finally, I discuss how personal research can lead to a higher degree.


Evaluation on the application of conjugate materials in the sound effect and stage effect of modern dance.
The emergence and application of conjugate materials provide a broader space for the performance of sound and presentation effects on the modern music stage. This article compared and analyzed the application of conjugated materials and traditional methods in modern dance sound effects and stage presentation effects through experiments, found that the application of conjugated materials on modern stages had the effect of enhancing visual effects. Its overall reflectivity, color saturation, brightness, transparency, etc. remain in the range of 78%-97%, which is better than traditional methods. In addition, the use of conjugated materials can also improve auditory performance, have greater penetration and durability, and reduce the impact of external noise; in terms of audience experience and dancer experience, the average proportions also reached 87.8893% and 89.3867% respectively. In addition, it also has high temperature resistance and antibacterial effects, with a maximum temperature resistance value of 314.28°C and an antibacterial effect of 95.86%, indicating that it can still maintain stability under high temperature conditions and has a good inhibitory effect on the proliferation of bacteria and viruses. These findings will lay the foundation for further expanding the application of conjugated materials on the modern dance stage.


Mutual effects of cationic ligands and substrate on activity of the Na+-transporting pyrophosphatase of Methanosarcina mazei.
The PP(i)-driven sodium pump (membrane pyrophosphatase) of Methanosarcina mazei (Mm-PPase) absolutely requires Na(+) and Mg(2+) for activity and additionally employs K(+) as a modulating cation. Here we explore relationships among Na(+), K(+), Mg(2+), and PP(i) binding sites by analyzing the dependency of the Mm-PPase PP(i)-hydrolyzing function on these ligands and protection offered by the ligands against Mm-PPase inactivation by trypsin and the SH-reagent mersalyl. Steady-state kinetic analysis of PP(i) hydrolysis indicated that catalysis involves random order binding of two Mg(2+) ions and two Na(+) ions, and the binding was almost independent of substrate (Mg(2)PP(i) complex) attachment. Each pair of metal ions, however, binds in a positively cooperative (or ordered) manner. The apparent cooperativity is lost only when Na(+) binds to preformed enzyme-Mg(2+)-substrate complex. The binding of K(+) increases, by a factor of 2.5, the catalytic constant, the Michaelis constant, and the Mg(2+) binding affinity, and these effects may result from K(+) binding to either one of the Na(+) sites or to a separate site. The effects of ligands on Mm-PPase inactivation by mersalyl and trypsin are highly correlated and are strongly indicative of ligand-induced enzyme conformational changes. Importantly, Na(+) binding induces a conformational change only when completing formation of the catalytically competent enzyme-substrate complex or a similar complex with a diphosphonate substrate analog. These data indicate considerable flexibility in Mm-PPase structure and provide evidence for its cyclic change in the course of catalytic turnover.


[Staphylococcus aureus bacteremia in the Dakar Fann University Hospital].
The purpose of this report was to describe epidemiological, clinical, and bacteriological findings in cases of Staphylococcus aureus bacteremia at the Infectious Diseases Clinic in Dakar. This retrospective study was carried out on data recorded between January 1, 1996 and December 31, 2002. The diagnosis of bacteremia was based on isolation of bacteria from blood culture. Bacterial susceptibility was studied with an antibiogram. Resistance to methicillin was assessed with a disk containing 5 microg of oxacillin on Mueller Hinton Agar containing 5% of NaCl. One hundred and thirty cases of S. aureus bacteremia were recorded. The mean age of patients was 31 years. Nosocomial bacteremia occurred in 22% of the cases. HIV infection was noted in 38 patients (29%). The death rate was 24%. Nosocomial and community-acquired strains were resistant to methicillin, respectively, in 72% and 51% of the cases. Bacteremias due to methicillin-resistant S. aureus strain were nosocomial infections in 23% of the cases. Most of the strains (80-100%) were susceptible to fusidic acid, gentamycin, erythromycin, and pefloxacin. All of them were susceptible to vancomycin. Such a high rate of MRSA bacteremia, in particular among nosocomial bacteremia, makes it essential to reinforce preventive measures in our hospitals and to provide them with effective drugs against MRSA, such as vancomycin.


Risk factors of direct heat-related hospital admissions during the 2009 heatwave in Adelaide, Australia: a matched case-control study.
The extreme heatwave of 2009 in South Australia dramatically increased morbidity, with a 14-fold increase in direct heat-related hospitalisation in metropolitan Adelaide. Our study aimed to identify risk factors for the excess morbidity. A matched case-control study of risk factors was conducted. Patients and matched community controls were interviewed to gather data on demographics, living environment, social support, health status and behaviour changes during the heatwave. Cases were all hospital admissions with heat-related diagnoses during the 5-day heatwave in 2009. Controls were randomly selected from communities. Descriptive analyses, simple and multiple conditional logistic regressions were performed. Adjusted ORs (AORs) were estimated. In total, 143 hospital patients and 143 matched community controls were interviewed, with a mean age of 73 years (SD 21), 96% European ethnicity, 63% retired, 36% with high school or higher education, and 8% institutional living. The regression model indicated that compared with the controls, cases were more likely to have heart disease (AOR=13.56, 95% CI 1.27 to 144.86) and dementia (AOR=26.43, 95% CI 1.99 to 350.73). The protective factors included higher education level (AOR=0.48, 95% CI 0.23 to 0.99), having air-conditioner in the bedroom (AOR=0.12, 95% CI 0.02 to 0.74), having an emergency button (AOR=0.09, 95% CI 0.01 to 0.96), using refreshment (AOR=0.10, 95% CI 0.01 to 0.84), and having more social activities (AOR=0.11, 95% CI 0.02 to 0.57). Pre-existing heart disease and dementia significantly increase the risk of direct heat-related hospitalisations during heatwaves. The presence of an air-conditioner in the bedroom, more social activities, a higher education level, use of emergency buttons and refreshments reduce the risk during heatwaves.


Management of exaggerated gagging in prosthodontic patients using glossopharyngeal nerve block.
When gag reflex becomes abnormally active, it poses difficulty for the prosthodontists, as it hinders the process of fixed partial denture construction beginning with tooth preparation till impression making. In this case-report, the authors used a nerve block technique which is popular among anaesthetist and otolaryngologist, but is being applied in the field of prosthodontics for the first time, to tide over the difficulty.


RANTES levels in peripheral blood, CSF and contused brain tissue as a marker for outcome in traumatic brain injury (TBI) patients.
Traumatic brain injury (TBI) causes activation of several neurochemical and physiological cascades, leading to neurological impairment. We aimed to investigate the level of novel chemokine RANTES in plasma, cerebrospinal fluid (CSF) and contused brain tissue in traumatic brain injury patients and to correlate the expression of this chemokine with the severity of head injury and neurological outcome. This longitudinal case control study was performed on 70 TBI patients over a period of 30 months. Glasgow coma scale (GCS) and Glasgow outcome score were used to assess the severity of head injury and clinical outcome. Level of RANTES was quantified in plasma (n = 60), CSF (N = 10) and contused brain tissue (n = 5). Alterations in the plasma levels on 1st and 5th day following TBI were assessed. Patients were categorized as severe (GCS < 8) (SHI), moderate and mild Head injury (GCS > 8-14). 15 healthy volunteers were taken as the control group. The median plasma RANTES levels were 971.3 (88.40-1931.1); 999.2 (31.2-2054.9); 471.8 (370.9-631.9) for SHI, MHI and healthy control respectively and showed statistically significant variation (p = 0.005). There was no statistical difference in the mean 1st and 5th day RANTES levels for the SHI group. However, admission RANTES levels were significantly higher in patients who died than those who survived (p = 0.04). Also, RANTES levels were significantly higher in plasma as compared to contused brain tissue and CSF (p = 0.0001). This is the first study of its kind which shows that there is significant correlation of admission RANTES levels and early mortality. Another interesting finding was the significant upregulated in the expression of RANTES in plasma, compared to CSF and contused brain tissue following severe TBI.


Pituitary-gonadal response to gonadotropin-releasing hormone stimulation is enhanced in men after strenuous physical exercise.
The effects of strenuous physical exercise were studied on the pituitary-testicular response to gonadotropin-releasing hormone (GnRH) stimulation and on growth hormone (GH) and cortisol secretion. Eight healthy adult males were injected twice intravenously with 0.1 mg of GnRH at intervals of 21 days. At the time of the first injection (exercise trial) the subjects had been bicycling for 4 h on the road, and at the time of the second injection (rest trial) they had been resting in a sitting position for 4 h. Blood samples were taken before and after the 4-h period and 30, 60 and 120 min after the GnRH injection. Both testosterone and luteinizing hormone (LH) decreased during the exercise by 18% (p = 0.037) and 29% (p = 0.0028), respectively, but increased after the GnRH injection by 1.4- and 12.9-fold (p = 0.0001 for both). The areas under the testosterone and LH response curves after GnRH were significantly larger in the exercise trial than in the rest trial, threefold (p = 0.013) and 1.3-fold (p = 0.0007), respectively. Growth hormone and cortisol increased during the exercise trial. In the rest trial, the GnRH injection increased serum GH concentrations (p = 0.027). In conclusion, the diminished hypothalamic GnRH secretion seems to be the major cause of the post-exercise decrease in LH and testosterone, but altered sensitivity of the pituitary to GnRH also may be involved. Apparently, the build-up of pituitary LH stores during exercise explains the enhanced LH and testosterone response to GnRH challenge after exercise in comparison to control GnRH challenge.


Do Immigrants' Health Advantages Remain After Unemployment? Variations by Race-Ethnicity and Gender.
Immigrants tend to display more favorable health outcomes than native-born co-ethnics. At the same time, they face considerable employment instability. It is unclear whether immigrants' job conditions may compromise their health advantage. Using U.S. National Health Interview Survey data, this study shows that the experience of unemployment reduces immigrants' health advantage, but unemployed foreign-born Blacks, White women, and Asian women still have lower mortality rates than their native-born employed counterparts. Overall, unemployment is less detrimental to immigrants than to natives, and immigrants' "survival advantage after unemployment" persists as their duration of residence extends. We further find substantial heterogeneity in the unemployment effect within immigrants. Asian immigrants display a much sharper gender difference in the mortality consequence of unemployment than other immigrants. Asian men's worse general health and substantially higher smoking rate, especially among the unemployed, lead them to fare much worse than Asian women following unemployment.


Thyroid function, endothelium, and inflammation in hemodialyzed patients: possible relations?
Renal function affects the thyroid gland in many ways. Disturbances in hemostasis and inflammation are common complications of kidney diseases. Endothelial dysfunction may link these two processes. A cross-sectional study on thyroid hormones in relation to markers of endothelial damage and inflammation in 96 hemodialyzed (HD) patients and 39 healthy volunteers was performed. The study took place in the dialysis unit at a university hospital. Thyroid hormones, markers of endothelial damage (von Willebrand factor, thrombomodulin, intracellular adhesion molecule, and CD146), markers of inflammation (high-sensitivity C-reactive protein, tumor necrosis factor alpha), other hemostatic parameters (thrombin-antithrombin complexes, prothrombin fragments 1 + 2 - F1 + 2, plasmin-antiplasmin complexes, tissue plasminogen activator and its inhibitor, tissue factor pathway inhibitor, and platelet glycoprotein V) were measured using commercially available kits. Free T3 and total T3 were lower in HD patients compared with controls. Markers of endothelial dysfunction and inflammation were significantly elevated in HD patients compared with controls. In multiple regression analysis T3 was independently related to time on dialyses, albumin, iron, ferritin, C-reactive protein (CRP), and F1 + 2 in HD patients. Free T3 was also independently related to total protein, total calcium, and triglycerides. In patients with CRP less than 6 mg/L in multiple regression analysis the only correlates of T3 were albumin and ferritin, whereas the only correlates of free T3 were albumin and time on dialyses. Multiple regression analysis showed that in HD patients with CRP greater than equal to 6 mg/L predictors of free T3 were CRP, F1 + 2, and dose of erythropoietin. In healthy volunteers T3 was related to tissue factor pathway inhibitor and platelet glycoprotein V was related to thyroid-stimulating hormone. We described novel relations between thyroid hormones and markers of endothelial dysfunction and inflammation in HD patients. Thyroid dysfunction is related to time on dialyses, endothelial damage, and inflammatory state, frequently encountered in uremia. Therefore, the relations between thyroid axis and endothelium in HD subjects merit additional studies.


Bladder cancer cells re-educate TAMs through lactate shuttling in the microfluidic cancer microenvironment.
In the present study, we aimed to investigate the influence of lactate shuttling on the functional polarization and spatial distribution of transitional cell carcinoma of the bladder (TCCB) cells and macrophages. We designed a microfluidic coculture chip for real-time integrative assays. The effect of lactate shuttling on the re-education of macrophages by TCCB cells was explored by measuring the levels of NO using a total NO assay kit and by evaluating the protein expression of iNOS, p-NFkB-p65, Arg-1 and HIF-1α via cell immunofluorescence and western blotting. Additionally, we examined TCCB cell viability using acridine orange/ethidium bromide (AO/EB) and MitoTracker staining. Moreover, the concentration distributions of lactate and large signaling proteins in the culture chambers were measured using 4',6-diamidino-2-phenylindole (DAPI) and fluorescein isothiocyanate-dextran (FITC-dextran). Furthermore, the recruitment of macrophages and the influence of macrophages on BC metastasis were observed via light microscopy. We confirmed that TCCB cells reprogrammed macrophages into an M2 phenotype. Moreover, lactate inhibited M1 polarization and induced M2 polarization of macrophages, but blockade of cancer cell-macrophage lactate flux significantly inhibited the re-education of macrophages by TCCB cells. In addition, lactate diffused faster and deeper than large signaling proteins in the microfluidic tumor microenvironment. Furthermore, lactate alone induced the migration of macrophages, and M1, but not M2, macrophages reduced the motility of TCCB cells. TCCB cells reprogrammed macrophages into an M2 phenotype in a manner that depended on cancer cell-TAM lactate flux. Furthermore, the lactate shuttle may be a determinant of the density of TAMs in tumor tissue.


Wernicke-Korsakoff syndrome (WKS) in Australia: no room for complacency.
Australia has made a substantial contribution to the recognition and treatment of the Wernicke-Korsakoff syndrome (WKS). Much of this occurred over a generation ago, and vigilance in identifying this condition needs to be sustained. More recently, treatment protocols have been developed by the Royal College of Physicians (London). These provide guidelines on when and how to treat both patients at risk and those with acute Wernicke's encephalopathy (WE). It is not known how widespread these recommendations have been applied in Australia. We highlight these current treatment guidelines and illustrate management issues with two case reports. A decline in treatment practices in the United Kingdom prompted the development of these guidelines. Current treatment practices in Australia have not been reported. All alcohol and drug workers need to be reminded regularly of this condition and the need for prompt recognition and treatment.


Neural control of the endocrine rat heart.
Although atrial stretch is the accepted stimulus for atrial natriuretic factor (ANF), in vivo studies suggest a stretch-independent, neurally induced ANF release mechanism. Thus the hypothesis that cardiac nerves can stimulate ANF secretion was tested in the Langendorff-perfused, paced rat heart. Venom from the scorpion Centruroides sculpturatus was used to activate neuronal sodium channels, veratridine was added to activate sodium channels (predominantly in myocytes), and electrical stimulation was applied to the right atrial appendage. The efficacy of nerve stimulation was verified by measurements of increased neuropeptide Y in the effluent. ANF levels in the effluent increased by 120% over baseline with 0.5 microM scorpion venom and by 88% with 0.5 microM veratridine (P < 0.01). Cardiac mechanics did not explain the large, concentration-dependent ANF response to the scorpion venom, since changes in the left ventricular developed pressure were small, opposite to those induced by veratridine, and unaffected by sympathectomy or adrenergic receptor blockade. Prior chemical sympathectomy and adrenergic receptor blockade almost abolished the ANF response to scorpion venom but hardly affected the ANF response to veratridine. Addition of 1 microM tetrodotoxin abolished all ANF responses. Electrical stimulation of the atrial appendage increased the ANF secretion by 60.2% (P < 0.02), in conjunction with neuropeptide Y, whereas control stimulations were ineffective. These studies unequivocally demonstrate that stimulation of cardiac sympathetic nerves potently stimulates ANF secretion.


Nitrogen and Phosphorus Signaling and Transport During Legume-Rhizobium Symbiosis.
Nitrogen (N) and phosphorus (P) are the two predominant mineral elements, which are not only essential for plant growth and development in general but also play a key role in symbiotic N fixation in legumes. Legume plants have evolved complex signaling networks to respond to both external and internal levels of these macronutrients to optimize symbiotic N fixation in nodules. Inorganic phosphate (Pi) and nitrate (NO3 -) are the two major forms of P and N elements utilized by plants, respectively. Pi starvation and NO3 - application both reduce symbiotic N fixation via similar changes in the nodule gene expression and invoke local and long-distance, systemic responses, of which N-compound feedback regulation of rhizobial nitrogenase activity appears to operate under both conditions. Most of the N and P signaling and transport processes have been investigated in model organisms, such as Medicago truncatula, Lotus japonicus, Glycine max, Phaseolus vulgaris, Arabidopsis thaliana, Oryza sativa, etc. We attempted to discuss some of these processes wherever appropriate, to serve as references for a better understanding of the N and P signaling and transport during symbiosis.


Effect of the amino-oxazoline derivative S-3341 on pre- and postjunctional alpha-adrenoceptors in isolated blood vessels.
In segments of isolated dog saphenous veins, S-3341 (10(-8) to 10(-4) M) induced concentration-dependent contractions which, like those to clonidine, were progressively inhibited by increasing concentrations of yohimbine (10(-8) to 10(-6) M) but not by prazosin (10(-8) to 10(-6) M). In strips of the rabbit main pulmonary artery, previously labelled with [3H]noradrenaline and mounted for superfusion, S-3341 and clonidine both decreased the overflow of [3H] caused by electrical stimulation; these effects of S-3341 and clonidine were inhibited by 10(-6) M of yohimbine but not by 10(-6) M of prazosin. Our results illustrate that both S-3341 and clonidine cause contraction by activation of postjunctional alpha 2-adrenoceptors and decrease noradrenaline-release by stimulating prejunctional alpha 2-adrenoceptors. At the postjunctional alpha 2-adrenoceptors clonidine is 27 times more potent than S-3341, while at the prejunctional alpha 2-adrenoceptors, clonidine is only 15 times more potent than S-3341.


Lack of difference between retinoic acid and retinol in stimulating progesterone production by luteinizing granulosa cells in vitro.
Receptors for retinoids in the immature rat ovary and the effects of retinol and retinoic acid on luteinizing granulosa cells were studied. Radioreceptor assay demonstrated the presence of specific cellular retinol-binding protein and cellular retinoic acid-binding protein in the ovaries of rats injected with PMSG alone or PMSG and hCG. In addition, when luteinizing granulosa cell from PMSG/hCG-injected immature rats were cultured with or without retinoic acid, the morphology, viability, number of cells in culture, and progesterone (P) accumulation were not affected by up to 10 microM retinoic acid. Beyond 10 microM, the cells began to round up, which was associated with a decrease in cell viability. Surprisingly, the deleterious concentrations of retinoic acid increased progesterone accumulation significantly higher than the medium control value. This increase in progesterone, however, was not accompanied by an increase in cAMP. When cells preincubated for 2 days with 1 microM of either retinoic acid or retinol were subsequently incubated in retinoid-free medium containing various substrates for steroidogenesis, the following results were obtained. Basal progesterone and its accumulation in response to human low density lipoprotein were significantly higher in cells preincubated with retinoids than in the control cells. However, no difference was seen in the degree of stimulation between retinol and retinoic acid pretreatments. Both 25-hydroxycholesterol, a substrate for side-chain cleavage enzyme, and pregnenolone, a substrate for 3 beta-hydroxysteroid dehydrogenase, significantly stimulated the accumulation of progesterone in cells preincubated with retinoids over the control value. Again, no appreciable difference was observed between retinol and retinoic acid pretreatments. Our results suggest that receptors for retinoids are present in gonadotropin-primed immature rat ovaries, retinoids increase luteal cell progesterone accumulation, and no difference exists between retinol and retinoic acid in their ability to increase the accumulation of progesterone by these cells.


In silico, in vitro, and ex vivo studies of the toxicological and pharmacological properties of the flavonoid 5,7-dihydroxy-3,8,4'-trimethoxy.
Phytochemical studies of the species Pavonia glazioviana were performed. Quercetin, kaempferol, acacetin, and trimethoxylated flavonoid compounds (which present biological activity) were isolated. We aimed to evaluate the in silico, in vitro, and ex vivo toxicity of flavonoid 5,7-dihydroxy-3,8,4'-trimethoxy (Pg-1) obtained from P. glazioviana through chemical structure analyses, toxicity assessment, and predictive bioactive properties, using human samples in in vitro tests. In silico analysis suggested that Pg-1 presents a good absorption index for penetrating biological membranes (for oral bioavailability), while also suggesting potential antimutagenic, anticarcinogenic, antioxidant, antineoplastic, anti-inflammatory, anti-hemorrhagic, and apoptosis agonist bioactivities. Assessment of hemolytic and genotoxic effects revealed low hemolysis rates in red blood cells with no cellular toxicity in oral mucosa cells. The reduced cytotoxic activity suggested the safety of the concentrations used (500-1000 µg/mL), and demonstrated the varied interactions of Pg-1 with the analyzed cells. The data obtained in the present study suggested potential therapeutic application, and the non-toxic profile indicated viability for future studies.


Documenting Community Health Worker Roles in Primary Care: Contributions to Evidence-Based Integration Into Health Care Teams, 2015.
The Patient Protection and Affordable Care Act provided community health workers (CHWs) with new opportunities, and current efforts develop evidence-based guidelines for CHW integration into clinical teams. This qualitative study documents CHW roles and activities in 3 federally qualified health care centers in southern Arizona. Community health worker clinical roles, activities, and integration varied by health center and were in flux. Integration included complementary roles, scheduled and everyday communications with team members, and documentation in the electronic health records. These findings contribute to evidence-based guidelines for CHW integration into clinical teams that are critical to maximizing CHW contributions to patient health improvements.


Sign language acquisition in a mute autistic boy.
A mute autistic boy learned to communicate extensively through American Sign Language. Over a six-month period he produced many spontaneous signs and sign combinations, and analyses of child's sign combinations indicated the presence of a full range of semantic relations. Further evidence of conceptual progress was provided by the child's increased score on the Peabody Picture Vocabulary Test. In addition, parents' and teacher's reports indicated that the child's social behavior improved. The extent of the boy's linguistic progress and associated improvement in social behavior markedly exceeds that usually reported for mute autistic children.


Early detection and diagnosis of neurobehavioral disorders associated with cancer and its treatment.
The cognitive and behavioral disorders associated with cancer and its treatments can have a tremendous impact on patients' quality of life. Brain tumors, leptomeningeal disease, and paraneoplastic syndromes have all been shown to cause specific neurobehavioral abnormalities. In addition, cancer patients frequently develop cognitive and behavioral alterations during or after radiation therapy, chemotherapy, or immunotherapy. Although some impairments are acute and reversible, others may persist after the cessation of treatment or have a delayed onset. These neurobehavioral disorders can range from profound intellectual decline (dementia) to subtle deficits evident only on sensitive neuropsychological tests. Even mild cognitive impairments may compromise an individual's ability to return to work or other activities.


The art of pain management.
Pain assessment is fundamental to the successful management of pain. Effective communication, in particular the use of empathy, underpins assessment. Concepts within the art of nursing can usefully be applied to the understanding of pain.


Effects of alcohol on person perception: a social cognitive neuroscience approach.
The acute effects of alcohol on cognitive processing of expectancy violations were investigated using event-related brain potentials and a cued recall task to index attentional and working memory processes associated with inconsistency resolution. As predicted, expectancy-violating behaviors elicited larger late positive potentials (LPP) and were recalled better than expectancy-consistent behaviors. These effects were moderated by alcohol and the valence of initial expectancies. For placebo group participants, positive targets performing negative behaviors elicited the largest LPP responses and were recalled best. For those in the alcohol groups, negative targets behaving positively elicited the largest LPP and recall responses. These findings suggest that alcohol does not globally impair working memory processes in person perception but instead changes the nature of valenced information processing. Findings are discussed in the context of alcohol's effects on working memory processes, reward sensitivity, and the prefrontal cortical structures thought to mediate them.


A robust method for transcript quantification with RNA-seq data.
The advent of high throughput RNA-seq technology allows deep sampling of the transcriptome, making it possible to characterize both the diversity and the abundance of transcript isoforms. Accurate abundance estimation or transcript quantification of isoforms is critical for downstream differential analysis (e.g., healthy vs. diseased cells) but remains a challenging problem for several reasons. First, while various types of algorithms have been developed for abundance estimation, short reads often do not uniquely identify the transcript isoforms from which they were sampled. As a result, the quantification problem may not be identifiable, i.e., lacks a unique transcript solution even if the read maps uniquely to the reference genome. In this article, we develop a general linear model for transcript quantification that leverages reads spanning multiple splice junctions to ameliorate identifiability. Second, RNA-seq reads sampled from the transcriptome exhibit unknown position-specific and sequence-specific biases. We extend our method to simultaneously learn bias parameters during transcript quantification to improve accuracy. Third, transcript quantification is often provided with a candidate set of isoforms, not all of which are likely to be significantly expressed in a given tissue type or condition. By resolving the linear system with LASSO, our approach can infer an accurate set of dominantly expressed transcripts while existing methods tend to assign positive expression to every candidate isoform. Using simulated RNA-seq datasets, our method demonstrated better quantification accuracy and the inference of dominant set of transcripts than existing methods. The application of our method on real data experimentally demonstrated that transcript quantification is effective for differential analysis of transcriptomes.


Chronic counterpulsation with descending thoracic aortomyoplasty improved cardiac function in animals with heart failure.
Descending thoracic aortomyoplasty uses latissimus dorsi muscle for extraaortic diastolic counterpulsation. We hypothesized that descending thoracic aortomyoplasty could improve ventricular function in dogs (n = 5) with heart failure. The left latissimus dorsi muscle was wrapped around the descending aorta and conditioned for 4 weeks with a burst stimulator (five pulses, 33 Hz, 28 bursts/min). Heart failure was induced by rapid ventricular pacing after conditioning. Left ventricular volume was measured with a conductance catheter. Left ventricular and aortic pressures were measured with a micromanometer. Mean diastolic blood pressure, endocardial viability ratio, left ventricular peak pressure, left ventricular end-diastolic pressure, stroke work, isovolumic relaxation time constant, and the end-systolic pressure volume relation were measured at baseline (after heart failure) and with the descending thoracic aortomyoplasty stimulated at 1:1. Contraction of the descending thoracic aortomyoplasty augmented mean diastolic blood pressure (62 +/- 4 to 71 +/- 3 mm Hg) and endocardial viability ratio (1.0 +/- 0.30 to 1.5 +/- 0.13) (p < 0.05). Left ventricular peak pressure (98 +/- 4 to 88 +/- 3 mm Hg), left ventricular end-diastolic pressure (19 +/- 4 to 14 +/- 4 mm Hg), and stroke work (1048 +/- 124 to 743 +/- 80 mm Hg.cm3) (p < 0.05) were reduced. The end-systolic pressure volume relation increased with descending thoracic aortomyoplasty stimulation (3.7 +/- 0.7 to 4.5 +/- 0.8 mm Hg/mL), and the isovolumic diastolic relaxation time constant significantly decreased (54 +/- 6 to 49 +/- 7 msec) (p < 0.05). We conclude that descending thoracic aortomyoplasty can provide diastolic counterpulsation and reduce stroke work in animals with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)


Global Proteomic Analyses Reveals Abnormal Immune Regulation in Patients With New Onset Ankylosing Spondylitis.
Ankylosing spondylitis (AS) is a chronic inflammatory disease with serious consequences and a high rate of morbidity and mortality, In our previous work, we reveal the key features of proteins in new-onset ankylosing spondylitis patients. Ankylosing spondylitis (AS) is a chronic inflammatory condition that affects the spine, and inflammation plays an essential role in AS pathogenesis. The inflammatory process in AS, however, is still poorly understood due to its intricacy. Systematic proteomic and phosphorylation analyses of peripheral blood mononuclear cells (PBMCs) were used to investigate potential pathways involved in AS pathogenesis. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was performed and discovered 782 differentially expressed proteins (DEPs) and 122 differentially phosphorylated proteins (DPPs) between 9 new-onset AS patients and 9 healthy controls. The DEPs were further verified using parallel reaction monitoring (PRM) analysis. PRM analysis verified that 3 proteins (HSP90AB1, HSP90AA1 and HSPA8) in the antigen processing and presentation pathway, 6 proteins (including ITPR1, MYLK and STIM1) in the platelet activation pathway and 10 proteins (including MYL12A, MYL9 and ROCK2) in the leukocyte transendothelial migration pathway were highly expressed in the PBMCs of AS patients. The key proteins involved in antigen processing and presentation, platelet activation and leukocyte transendothelial migration revealed abnormal immune regulation in patients with new-onset AS. These proteins might be used as candidate markers for AS diagnosis and new therapeutic targets, as well as elucidating the pathophysiology of AS.


The inadequate effect of automobile seating on foot posture and callus development.
Driver posture is an important factor to be considered in the ergonomics design process of automobiles. Most decisions during automobile design and manufacture are informed by studying the intricate biomechanical components of human musculoskeletal systems to ensure maximum comfort, safety and well-being during driving. A case study is presented that confirms inappropriate foot position as a causative factor for the development of abnormal lateral/plantar heel callosities when driving a 4 x 4-style vehicle. The driver's foot position was influenced by the seat geometry of the vehicle. Cessation of driving the 4 x 4-style vehicle and driving of an alternative automobile while on holiday for a period of 4 weeks resolved the condition. On return to the 4 x 4-style vehicle, however, the abnormal callus patterns redeveloped while using the same footwear and no change in any other parameters. It is therefore suggested that seat and consequent foot position is an important ergonomic factor that should be addressed in the future design of automobile seating.


Immunohistochemical staining for apolipoprotein B in human sarcomas.
A study of immunocytochemical staining for apolipoprotein B (apo B) in 52 human sarcomas and eight benign soft-tissue tumors is described. A peroxidase-antiperoxidase technique was employed using a rabbit anti-apo B antiserum. All 27 liposarcomas examined were positive for apo B, and 23 of these tumors showed at least 2-plus staining on a scale of 0 to 3 plus. Of the ten myxoid liposarcomas within this group, seven showed 2-plus or 3-plus staining, while the other three stained 1 plus. By contrast, 11 of 13 malignant fibrous histiocytomas were negative for apo B; the remainder showed 1-plus staining. Myxoid areas present in three of these cases were negative for apo B. Five of seven rhabdomyosarcomas stained at least 2 plus for apo B. Both benign and malignant peripheral nerve sheath tumors showed no consistent pattern of staining. We conclude that apo B immunocytochemical staining tends to be high in tumors whose normal tissue counterparts exhibit relatively large numbers of low-density lipoprotein receptors. Furthermore, immunoperoxidase staining for apo B should be a useful adjunct in the evaluation of soft-tissue sarcomas, particularly in cases with myxoid differentiation.


A retrospective evaluation of analgesic exposures from Izmir, Turkey.
The objective of this study is to analyze exposures concerning analgesics that were reported to Dokuz Eylul University Drug and Poison Information Center (DPIC) and admitted to the Department of Emergency Medicine in Dokuz Eylul University Hospital (EMDEU) between 1993 and 2004. Demographics of the patients, characteristics of analgesic exposures, performed treatment attempts and outcome of the poisoned patients were recorded on standard data forms and were then entered into a computerized database program. Statistical analysis was performed by using the chi-square test. The DPIC recorded 55 962 poisoning calls, 48 654 (86.9%) of them related to medicines. Analgesics accounted for 16.3% (7 939 cases) of all medicine-related exposures; among them 446 exposures were admitted to EMDEU. More than half of the analgesic exposure calls and admitted cases involved adults (55.9%, 4 440). Females dominated in all age groups (70.3%, 5 578). Mean age was 20.2 +/- 11.8. The most involved analgesics were paracetamol (47.9%), propionic acid derivatives (16.1%) and salicylates (13.7%). Most of the poisonings were intentional (75.1%), especially in 19-29 years age group of adults and 13-18 years age group of children. Most of the patients reported to DPIC and admitted to EMDEU were asymptomatic (84.4% and 54.7%, respectively). Gastrointestinal decontamination methods were performed more frequently for admitted poisoning cases before hospital admission than reported poisoning cases (61% vs. 23%). Paracetamol ingestion was the most common cause of analgesic exposures reported to our DPIC. Most of the analgesic exposures reported to DPIC were asymptomatic or mild. DPICs have an important role for the referral of analgesic exposures without unnecessary gastrointestinal decontamination procedures.


Prognosis Prediction of Uveal Melanoma After Plaque Brachytherapy Based on Ultrasound With Machine Learning.
Uveal melanoma (UM) is the most common intraocular malignancy in adults. Plaque brachytherapy remains the dominant eyeball-conserving therapy for UM. Tumor regression in UM after plaque brachytherapy has been reported as a valuable prognostic factor. The present study aimed to develop an accurate machine-learning model to predict the 4-year risk of metastasis and death in UM based on ocular ultrasound data. A total of 454 patients with UM were enrolled in this retrospective, single-center study. All patients were followed up for at least 4 years after plaque brachytherapy and underwent ophthalmologic evaluations before the therapy. B-scan ultrasonography was used to measure the basal diameters and thickness of tumors preoperatively and postoperatively. Random Forest (RF) algorithm was used to construct two prediction models: whether a patient will survive for more than 4 years and whether the tumor will develop metastasis within 4 years after treatment. Our predictive model achieved an area under the receiver operating characteristic curve (AUC) of 0.708 for predicting death using only a one-time follow-up record. Including the data from two additional follow-ups increased the AUC of the model to 0.883. We attained AUCs of 0.730 and 0.846 with data from one and three-time follow-up, respectively, for predicting metastasis. The model found that the amount of postoperative follow-up data significantly improved death and metastasis prediction accuracy. Furthermore, we divided tumor treatment response into four patterns. The D(decrease)/S(stable) patterns are associated with a significantly better prognosis than the I(increase)/O(other) patterns. The present study developed an RF model to predict the risk of metastasis and death from UM within 4 years based on ultrasound follow-up records following plaque brachytherapy. We intend to further validate our model in prospective datasets, enabling us to implement timely and efficient treatments.


Comparison of Intravenous Versus Nebulized Dexmedetomidine for Laryngoscopy and Intubation-Induced Sympathoadrenal Stress Response Attenuation.
Nebulized dexmedetomidine has been used for procedural sedation and allaying separation anxiety in children. Literature regarding its use in the attenuation of laryngoscopy and intubation response via the nebulized route is scarce. We evaluated preoperative dexmedetomidine nebulization on the hemodynamic response arising from laryngoscopy/intubation, hemodynamics, analgesic consumption, and postoperative sore throat. The primary objective was to evaluate/compare the hemodynamic effects of preoperative intravenous and nebulized dexmedetomidine on laryngoscopy/intubation and compare the efficacy of the two routes in blunting the sympathoadrenal response. The secondary objective was to evaluate their effects on intraoperative analgesic consumption and incidence and sore throat postoperatively. 120 ASA I & II adult patients undergoing elective surgeries requiring tracheal intubation were randomized to receive intravenous dexmedetomidine (1 µg/kg over 10 minutes) and nebulized dexmedetomidine (1 µg/kg in 3 - 4 mL of 0.9% saline), 30 min before anesthesia induction. Heart rate and non-invasive blood pressure were monitored for 10 min following laryngoscopy and then throughout the surgery. Intraoperative analgesic consumption, postoperative sore throat, and recovery from anesthesia were assessed. No significant hemodynamic difference was found between the two groups till three minutes. Then, the difference turned significant owing to a greater fall in the heart rate and mean arterial pressure in the intravenous group. Nebulized dexmedetomidine exhibited a lesser tendency of hypo/hypertension and brady/tachycardia, while hemodynamics was more stable. There was lesser sore throat and sedation in the nebulized group. Intraoperative analgesic and propofol consumption was comparable between the two groups. Nebulized dexmedetomidine attenuated laryngoscopy and intubation response, although to a lesser extent than the intravenous group in equivalent doses. However, the nebulized route provided greater hemodynamic stability in the intraoperative period and lesser sedation/sore throat postoperatively without an increase in adverse effects. Nebulized dexmedetomidine may provide a more holistic and viable alternative in patients who poorly tolerate hypotension, bradycardia, and sedation.


Allylmethylsulfide, a Sulfur Compound Derived from Garlic, Attenuates Isoproterenol-Induced Cardiac Hypertrophy in Rats.
Allylmethylsulfide (AMS) is a novel sulfur metabolite found in the garlic-fed serum of humans and animals. In the present study, we have observed that AMS is safe on chronic administration and has a potential antihypertrophic effect. Chronic administration of AMS for 30 days did not cause any significant differences in the body weight, electrocardiogram, food intake, serum biochemical parameters, and histopathology of vital organs. Single-dose pharmacokinetics of AMS suggests that AMS is rapidly metabolized into Allylmethylsulfoxide (AMSO) and Allylmethylsulfone (AMSO2). To evaluate the efficacy of AMS, cardiac hypertrophy was induced by subcutaneous implantation of ALZET® osmotic minipump containing isoproterenol (~5 mg/kg/day), cotreated with AMS (25 and 50 mg/kg/day) and enalapril (10 mg/kg/day) for 2 weeks. AMS and enalapril significantly reduced cardiac hypertrophy as studied by the heart weight to body weight ratio and mRNA expression of fetal genes (ANP and β-MHC). We have observed that TBARS, a parameter of lipid peroxidation, was reduced and the antioxidant enzymes (glutathione, catalase, and superoxide dismutase) were improved in the AMS and enalapril-cotreated hypertrophic hearts. The extracellular matrix (ECM) components such as matrix metalloproteinases (MMP2 and MMP9) were significantly upregulated in the diseased hearts; however, with the AMS and enalapril, it was preserved. Similarly, caspases 3, 7, and 9 were upregulated in hypertrophic hearts, and with the AMS and enalapril treatment, they were reduced. Further to corroborate this finding with in vitro data, we have checked the nuclear expression of caspase 3/7 in the H9c2 cells treated with isoproterenol and observed that AMS cotreatment reduced it significantly. Histopathological investigation of myocardium suggests AMS and enalapril treatment reduced fibrosis in hypertrophied hearts. Based on our experimental results, we conclude that AMS, an active metabolite of garlic, could reduce isoproterenol-induced cardiac hypertrophy by reducing oxidative stress, apoptosis, and stabilizing ECM components.


Quantitative detection of trichloroacetic acid in human urine using isotope dilution high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.
The chemical disinfection of drinking water to control microbial contaminants results in the formation of disinfection byproducts (DBPs). The volatile trihalomethanes and the nonvolatile haloacetic acids (HAAs) are the most prevalent DBPs. It is important to monitor human exposure to HAAs because of their potential adversehealth effects, such as cancer. Among the HAAs, urinary trichloroacetic acid (TCAA) is a potential valid biomarker for assessing chronic ingestion exposure to HAAs from drinking water. We have developed a rugged, high-throughput, sensitive, accurate, and precise assay for the measurement of trace levels of TCAA in human urine using a simple solid-phase extraction (SPE) cleanup followed by isotope dilution high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). TCAA is extracted from the urine using SPE, separated from other extract components by reversed-phase HPLC, and analyzed by negative ion electrospray ionization-isotope dilution-MS/MS using a multiple reaction monitoring experiment. The method is simple and fast and is not labor intensive (sample preparation and analysis can be performed in approximately 15 min) with a limit of detection of 0.5 ng/mL in 1 mL of urine.


Structural Stability of Diffusion Barriers in Cu/Ru/MgO/Ta/Si.
Various structures of Cu (50 nm)/Ru (2 nm)/MgO (0.5-3 nm)/Ta (2 nm)/Si were prepared by sputtering and electroplating techniques, in which the ultra-thin trilayer of Ru (2 nm)/MgO (0.5-3 nm)/Ta (2 nm) is used as the diffusion barrier against the interdiffusion between Cu film and Si substrate. The various structures of Cu/Ru/MgO/Ta/Si were characterized by four-point probes for their sheet resistances, by X-ray diffractometers for their crystal structures, by scanning electron microscopes for their surface morphologies, and by transmission electron microscopes for their cross-section and high resolution views. The results showed that the ultra-thin tri-layer of Ru (2 nm)/MgO (0.5-3 nm)/Ta (2 nm) is an effective diffusion barrier against the interdiffusion between Cu film and Si substrate. The MgO, and Ta layers as deposited are amorphous. The mechanism for the failure of the diffusion barrier is that the Ru layer first became discontinuous at a high temperature and the Ta layer sequentially become discontinuous at a higher temperature, the Cu atoms then diffuse through the MgO layer and to the substrate at the discontinuities, and the Cu₃Si phases finally form. The maximum temperature at which the structures of Cu (50 nm)/Ru (2 nm)/MgO (0.5-3 nm)/Ta (2 nm)/Si are annealed and still have low sheet resistance is from 550 to 750 °C for the annealing time of 5 min and from 500 to 700 °C for the annealing time of 30 min.


Bioinspired caries preventive strategy via customizable pellicles of saliva-derived protein/peptide constructs.
Dental caries has been the most widespread chronic disease globally associated with significant health and financial burdens. Caries typically starts in the enamel, which is a unique tissue that cannot be healed or regrown; nonetheless, new preventive approaches have limitations and no effective care has developed yet. Since enamel is a non-renewable tissue, we believe that the intimate overlaying layer, the acquired enamel pellicle (AEP), plays a crucial lifetime protective role and could be employed to control bacterial adhesion and dental plaque succession. Based on our identified AEP whole proteome/peptidome, we investigated the bioinhibitory capacities of the native abundant proteins/peptides adsorbed in pellicle-mimicking conditions. Further, we designed novel hybrid constructs comprising antifouling and antimicrobial functional domains derived from statherin and histatin families, respectively, to attain synergistic preventive effects. Three novel constructs demonstrated significant multifaceted bio-inhibition compared to either the whole saliva and/or its native proteins/peptides via reducing biomass fouling and inducing biofilm dispersion beside triggering bacterial cell death. These data are valuable to bioengineer precision-guided enamel pellicles as an efficient and versatile prevention remedy. In conclusion, integrating complementary acting functional domains of salivary proteins/peptides is a novel translational approach to design multifunctional customizable enamel pellicles for caries prevention.


[Not Available].
The pain of childbirth, whose description often link it closely to death phantasies, paralyzing fright and the fear of being torn apart, was integrated into a complex network of meanings in which ghosts and demons, personal misdemeanour, guilt, purification and initiation all had their place. Each individual interpretation of pain was supported by a variety of cultural meanings related to symbolic, metaphoric, popular religious, gender-specific, social and emotional significances. The meaningful components of these various meanings were not so much analyzed and discussed as incorporated into a code of conduct and creative practical application. On the one hand, by means of collective care and a staged joint overcoming of the pain, they robbed the experience of pain of its isolating prong and of the feeling of being at the mercy of a body both physically and imaginarily defenceless. At the same time they provided model interpretations for a variety of contexts; up as far as the mid-eighteenth century statements made while suffering from the pain of childbirth were assigned a high degree of truth; when assessing the quality and quantity of pain at childbirth, 'natural' pain was considered as initiation into motherhood, while excessive pain was seen as a punishment for concrete individual faults (violation of rules for pregnant women due to give birth) and a complete lack of pain as an indication of not wanting or not being able to be a mother (infanticides).


Prior induction of cellular antiviral pathways limits frog virus 3 replication in two permissive Xenopus laevis skin epithelial-like cell lines.
Frog virus 3 (FV3) causes mortality in a range of amphibian species. Despite the importance of the skin epithelium as a first line of defence against FV3, the interaction between amphibian skin epithelial cells and FV3 remains largely uncharacterized. Here, we used newly established Xenopus laevis skin epithelial-like cell lines, Xela DS2 and Xela VS2, to study the susceptibility and permissiveness of frog skin epithelial cells to FV3, and the innate immune antiviral and proinflammatory gene regulatory responses of these cells to FV3. Both cell lines are susceptible and permissive to FV3, yet do not exhibit appreciable transcript levels of scavenger receptors thought to be used by FV3 for cellular entry. Xela DS2 and Xela VS2 upregulate antiviral and proinflammatory cytokine transcripts in response to poly(I:C) but not to FV3 or UV-inactivated FV3. Poly(I:C) pretreatment limits FV3 replication and FV3-induced cytopathic effects in both cell lines. Thus, Xela DS2 and Xela VS2 can support FV3 replication, represent in vitro systems to investigate antiviral responses of frog skin epithelial cells, and can serve as novel tools for screening compounds that initiate effective antiviral programs to limit FV3 replication.


Tuning of T cell clone size and activation threshold by control of CD25 expression through mitogen-activated protein kinase pathways.
Following T cell receptor (TcR) engagement, CD25 expression is upregulated by T cells and controls their proliferation. It is not known how CD25 expression levels differentially influence T helper (Th) 1 and Th2 cell physiology. CD25 upregulation, and other T cell functions, were studied in human Th1 and Th2 clones following stimulation with various stimuli. The effects of pharmacological substances were then evaluated to identify the signaling pathways controlling CD25 upregulation. Upon TcR engagement, one Th2 clone was induced to express substantially more CD25 than a Th1 clone, although both clones downregulated CD3 with similar dose responses. It was also found that the amount of antigen needed to elicit proliferation and cytokine production was considerably lowered in the presence of interleukin-2 (IL-2) for the Th2 cells, while for the Th1 cells the threshold of activation was not modified by the presence of IL-2. It was then shown that PP2 and cyclosporin A strongly inhibited CD25 expression in both clones, while wortmannin and Ro-31-8220 had more limited effects. In contrast, mitogen-activated protein kinase (MAPK) inhibitors had strikingly different effects on CD25, blocking its expression in the Th2 cells, while augmenting it, or leaving it unaffected, in the Th1 cells. These unexpected observations suggested that in some T cells TcR-mediated activation of the MAPK pathways may inhibit CD25 expression rather than promoting it. Absence of this negative control mechanism may endow Th2 cells with a growth advantage over Th1 cells and their effector functions may be elicited at lower antigen doses.


Factors Governing and Application of the Cope Rearrangement of 3,3-Dicyano-1,5-dienes and Related Studies.
Cope and co-workers reported the [3,3] rearrangement of 3,3-dicyano-1,5-dienes in the early 1940s ("The Cope rearrangement"). However, these original substrates have remained largely unstudied until recently. Herein we explore styrene-deconjugating Cope rearrangements, a diastereoselective Cope rearrangement/deconjugative α-allylation sequence, and factors governing α- vs γ-allylation regioselectivity of Knoevenagel adduct allyl anions. Ultimately, these studies result in the synthesis of diverse and functionally dense polycycloalkane frameworks from abundant reagents using simple chemistry.


Smoking and skin: a study of the physical qualities and histology of skin in smokers and non-smokers.
Tobacco smoke is toxic to cells and could be a factor contributing to accelerated skin ageing. The aim of this study was to provide new information on the possible effects of smoking on the physical qualities of skin and the morphology of elastic fibres. The study population consisted of 98 men, including 47 current smokers and 51 never-smokers. Skin thickness and elasticity were measured from cheek, temple, abdomen, dorsal forearm and non-sun-exposed upper inner arm. Verhoeff-stained punch biopsies from the non-sun-exposed upper inner arm were assessed with a computerized image analyser in a blinded fashion to assess the amount and width of elastic fibres. The thickness of cheek skin was increased in the smokers, but skin thickness in other measured sites did not differ between the groups. The amount and width of elastic fibres in the sun-protected skin of the smokers and non-smokers did not differ significantly, nor did skin elasticity in this or any other region under evaluation, suggesting that smoking alone affects neither the amount and width of dermal elastic fibres nor the elasticity of skin in male smokers.


"A Good/Beautiful Word Is like a Good/Beautiful Tree..." From the Perspective of Creative Psychopharmacotherapy.
A good/beautiful word in creative psychopharmacotherapy offers: an environment for purposeful activities, such as creative work, structured work, enjoying the nature of essence and existence; and a feeling of security and safety, according to which it is necessary to act with respect and dignity, and permit the development of a feeling of belonging, value and trust; it is necessary to have time to express one's feelings to other members with sympathy, and active listening; the opportunity and encouragement for developing feelings and drawing conclusions from experience, including illness and its treatment; receiving permission and encouragement to develop a relationship with God or the Absolute; enable people to experience holiness, regardless of the time, place and privacy for prayer and worship; spiritual education, encouragement in faith, a feeling of universal connection and forgiveness.


Use of surface-immobilized Trichoderma in batch and fed-batch fermentations.
Needle-punch polyester was shown to be an effective support material for the immobilization of Trichoderma reesei Rut C30. When used as a resident inoculum for a batch process, the immobilized Trichoderma was very stable and resulted in a reduced rate of biomass generation in the bulk liquid phase as compared to cultures inoculated with free mycelium. Fed-batch fermentations with the immobilized Trichoderma produced ca. 80% of the activity of those using free cells; however, the activity was more stable and the crude enzyme broth produced had a greatly reduced biomass concentration.